Membrane attack complex (MAC) inhibitory factor (MACIF) is a 20-kD membrane protein that inhibits MAC formation on homologous cells. Until recently, a functional role of MACIF had been demonstrated in erythrocytes. Therefore, we have focused on the fact that glomerular epithelial cells (GECs) are the primary target of MAC-mediated damage in rat Heymann's nephritis model of human membranous nephropathy. Using immunocytochemistry and western blotting we have shown that MACIF is expressed in cultured human GECs. Phosphatidyl-inositol (PI)-phospholipase C (PLC) reduced MACIF expression in these cells, suggesting that MACIF is a PI-linked membrane protein in GECs. In addition, we elucidated that MACIF protects GECs against complement-mediated lysis. These findings suggest that MACIF expressed on GECs plays an important role in the protection of GECs against complement mediated-cellular damage in vivo.